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Environ Res. 2019 Oct;177:108593. doi: 10.1016/j.envres.2019.108593. Epub 2019 Jul 19.

Do stressful life events during pregnancy modify associations between phthalates and anogenital distance in newborns?

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Populations Studies Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada. Electronic address:
Populations Studies Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA.
School of Psychology, Centre de Recherche du CHU de Québec, Laval University, Quebec City, QC, Canada.
Research Axis, Brain and Child Development, CHU Sainte-Justine Research Center, Department of Psychiatry and Addiction, University of Montreal, Montreal, QC, Canada.
Department of Obstetrics & Gynaecology and School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.
Department of Pediatrics, University of Washington, Seattle, WA, USA.
Division of Perinatal Epidemiology Research Unit, Dalhousie University, Halifax, NS, Canada.
Clinical Research Unit, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
Department of Obstetrics & Gynecology, McGill University, Montreal, QC, Canada and RI-MUHC, Montreal, QC, Canada.
Head, Department of Obstetrics, Gynecology and Newborn Care, The Ottawa Hospital, Ottawa, ON, Canada.
Department of Obstetrics & Gynecology, University of Sherbrooke, Sherbrooke, QC, Canada.


Anogenital distance (AGD) has been used as a marker of fetal androgen action to identify endocrine disrupting chemicals. A US study (TIDES) has reported that the association between some phthalates and reduced AGD in males was only apparent in sons of mothers reporting no stressful life events (SLEs) during pregnancy. The objective of the current study was to examine the potential modifying effect of SLEs and their subjective impact on associations between prenatal phthalates and AGD. First trimester urines from the MIREC Study were analysed for phthalate metabolites and AGD was measured in neonates. Post-delivery, the women answered questions on SLEs during the pregnancy. Women reporting 1 or more SLEs during pregnancy were considered a "higher stressor" group, whereas women reporting no SLEs or who reported a SLE that was perceived as not at all stressful were considered a "lower stressor" group. Multivariable linear regression models were fit stratified by stressor group. Maternal stressor, AGD and phthalates results were available for 153 females and 147 males. A summary measure of androgen-disrupting phthalates (Σ AD) was associated with significantly longer AGDs in females from the higher stressor group. These effect sizes were increased when the perceived impact was restricted to moderately or very much stressful. In males, all phthalates were associated with longer anopenile distance (APD), regardless of stressor group; however, higher Σ AD was associated with significantly longer APD in the lower stressor group. In contrast to the TIDES study, we did not observe shorter AGDs in male infants prenatally exposed to di-(2-ethylhexyl) phthalates, regardless of maternal stressor level. In conclusion, we were unable to replicate the findings of the TIDES study, but did find some evidence that prenatal SLEs may modify associations between phthalates and female AGD. Further research with other populations and measures of prenatal stress may shed more light on whether prenatal stress is an important effect modifier of associations between phthalates (or other chemicals) and anogenital distance.


Anogenital distance; Phthalates; Pregnancy; Prenatal stress; Stressful life events

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